Successful generation of imageable microbubbles from what are expected to be much safer, very short, high amplitude acoustic pulses has increased the possibility of diagnostic, as well as therapeutic uses intravascular bubble generation addressed here. In addition, this project maintains a strong component of basic studies of methods of acoustic generation of microbubbles of desired properties in arterial blood, as well as studies of potential bioeffects relevant to a wide range of applications of medical ultrasound. This combined basic and applied approach is consistent with our strengths as a combined basic and clinical medical ultrasound science research group in a large academic and clinical medical center. Acoustic production in the blood of Bubbles from Ambient Gases (BAGs) and by vaporization of perfluorocarbon droplets will be pursued, with attention to physical factors controlling phase transition, size and dissolution. Experimental studies will evaluate the perfusion and infarction effects of size, number of bubbles and their longevity over ranges relevant to the proposed applications. The brain, and retina are chosen as the primary bioeffects study sites because those are among the most sensitive sites and offer diagnostic and therapeutic potential. Moving beyond the short, selective contrast bolus production being addressed at present, use of bubbles as point targets for correction of ultrasound beam distortions will be evaluated in the brain from bubbles introduced and generated in the carotid artery. Success will offer the possibility of very high resolution ultrasound imaging transcranially and in other areas accessible to ultrasound. Then flow occlusion for therapy will be developed and evaluated. Infarction of several centimeter tissue regions will be accomplished by bubble generation both in the treated volume and by occlusion of identifiable supply vessels. It is expected that this treatment will be faster, less expensive and/or less invasive than conventional angiography and surgery and comparable CT and MR techniques.